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In a collaborative study published in Nature Communications, researchers from Kunming Institute of Zoology, Chinese Academy of Sciences, and BGI have completed the genome sequencing of Chinese tree shrew, a small animal widely distributed in South Asia, Southeast Asia, and South and Southwest China. This work provides new insights for researchers to use tree shrew as a model in studying hepatitis C virus (HCV) and hepatitis B virus (HBV) infections, myopia, as well as social stress and depression.

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Tree shrews are similar to squirrels in their external appearance and habits. They have a higher brain to body mass ratio than any other mammals, and even than humans. Currently, tree shrews have been considered as a useful experimental model for researchers to design and develop new animal models for human diseases. However, the lack of a high-quality genome has greatly hampered the deeper understanding of this animal's biological features, evolutionary mechanisms, among others.

In this study, researchers conducted whole genome sequencing on a male Chinese tree shrew from Yunnan Province of China, and yielded a high-quality reference genome about 2.86Gb. Compared to the previous version reportedly in 2007, a significantly improved annotation was also generated, which contains 22,063 genes that is similar with the number of human genes. To identify the phylogenetic position of tree shrew in Euarchontoglires, they compared the tree shrew genome with other genomes, including human's, and revealed a closer relationship between tree shrew and primates.

When identifying the genetic features shared between tree shrew and primates, researchers found 28 genes previously considered as primate specific genes also present in tree shrew genome such as psoriasin protein and NKG2D ligands, indicating the tree shrew's immune system may employ the same indicators as in humans to eliminate infected and damaged cells. They also found some unique genetic features of tree shrew, such as immunoglobulin lambda variable gene family strikingly expanded to 67 copies in tree shrews but only 36 copies in the human genome.

Tree shrew has a well-developed brain structure that is similar with primate's. Researchers in this study detected 23 known neurotransmitter transporters in the tree shrew genome that are associated with the corresponding features of depression. These transporters are highly conserved in amino acid sequence with the human counterparts. All the findings provide a genetic basis for researchers making tree shrews an attractive model for experimental studies of psychosocial stress and evaluation of pharmacological effect of antidepressant drugs.

To understand the genetic basis underlying the visual system of tree shrew, researchers investigated the relevant genes involved in visual system, and found the tree shrew genome encompassed the orthologues of almost all the 209 known vision-related human genes. However, the lack of two cone photoreceptors, the middle wave-length sensitive proteins, may lead to the trichromacy in higher primates. The absence of these proteins is consistent with the fact that tree shrew is short of green pigment and possess dichromats, which is similar to some lower primates. Due to tree shrew's adaptation to the diurnal life, researchers found a looser evolutionary constraint of dim-light vision. Rod photoreceptor rhodopsin had a faster evolutionary rate in the tree shrew lineage, which is responsible for the night vision. A variant p.F45C that causes incurable night blindness disease in humans was detected in tree shrew species, suggesting a potentially functional degeneration of this gene in tree shrews.

The previous reports showed human HBV and HCV could infect tree shrew. Through investigating tree shrew immune genes associated with viral hepatitis, researchers found most of the genes respond in HBV and HCV infection showed a relatively high sequence identity between tree shrew and human genomes. They found the tree shrew lost DDX58, a key gene to produce interferon to against virus, and TRIM5 has achieved five Trim5 copies. One of TRIM5 copy has a CypA retrotranposition that present in only several primate species, implying the potential importance of this fused transcript.

Professor Yong-Gang Yao from Kunming Institute of Zoology, the leading author of this paper, said, "Since 1970s, researchers of our institute carried out many studies on the biology of Chinese tree shrews, and we published the first monograph of tree shrew in 1991. Currently, we are focused on establishing animal models of human diseases using this animal. The available genome data will greatly facilitate our efforts and speed up the process to design and develop new tree shrew models for human diseases, drug screening and safety testing"

Dr. Guojie Zhang, senior researcher from BGI, said, "The completion of tree shrew genome has solved long-term controversy regarding the phylogenetic position of tree shrew in Euarchontoglires. The genomic data in this study will also lay a solid genetic foundation for making tree shrew a viable animal model for better boosting medical research."

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The above story is based on materials provided by BGI Shenzhen. Note: Materials may be edited for content and length.

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